Analysis of immunosuppressive mechanism in neuroblastoma to develop a new treatment

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17548
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Chiba University
• Principal Investigator: Yoshizawa Hiroko 千葉大学, 医学部附属病院, 医員 (60814746)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 神経芽腫 / 樹状細胞 / NKT細胞

Outline of Final Research Achievements

To elucidate the mechanism that causes antitumor immunosuppression of dendritic cells under the existence of neuroblastoma cell line culture supernatant, a comprehensive analysis of gene and protein expression of dendritic cells and tumor cell lines was performed. To identify the soluble proteins secreted from neuroblastoma cell lines, all proteins in the culture supernatant were analyzed by proteomic analysis, and candidate proteins were identified. In addition, gene expression profiling of dendritic cells with or without culture supernatant was performed, and candidate genes that might be related to the suppression of anti-tumor immune responses were identified. We are currently investigating the mechanism of how these molecules suppress the anti-tumor immune response.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

近年、神経芽腫に対する新規治療として、腫瘍細胞表面に発現する糖脂質抗原Disialoganglioside (GD2) 抗原に対するモノクローナル抗体とIL-2、GM-CSFを併用した抗GD2抗体療法が、集学的治療を完了した高リスク神経芽腫の5年生存率を改善させることが報告されている。しかし、再発抑制に対する効果は限定的であり、未だ予後不良な患者が少なくない。本研究では、神経芽腫による抗腫瘍免疫抑制機序を解明し、抗腫瘍免疫の抑制状態を制御することで、より強力ながん免疫療法の新規開発を行うことを目的とする。この新規治療により予後が改善することで、神経芽腫の治療成績向上に貢献できる。